Obesity-associated cancer prevention
Authors: Sonja Chiappetta, Vincenzo Bottino
Journal: The Lancet Healthy Longevity (2023)

The Swedish Obese Subjects Study is one of the most important prospective studies in bariatric and metabolic surgery and has addressed many important scientific issues in the past. In the study by Kajsa Sjöholm and colleagues,1Sjöholm K Andersson-Assarsson JC Kristensson FM et al.Long-term incidence of haematological cancer after bariatric surgery or usual care in the Swedish Obese Subjects Study: a prospective cohort study.Lancet Healthy Longev. 2023; (published online Sept 13.)https://doi.org/10.1016/S2666-7568(23)00141-1Google Scholar the association between bariatric surgery and haematological cancer was analysed, and showed that bariatric surgery was associated with a reduced risk of haematological cancer and death due to haematological cancer with a follow-up of 33 years. To date, 13 types of obesity-associated malignant cancers (adenocarcinoma of the oesophagus, gastric cardia, colon and rectum, liver, gallbladder, pancreas, postmenopausal breast, corpus uteri, ovary, renal cell carcinoma, meningioma, thyroid, and multiple myeloma) have sufficient evidence to indicate a cancer-preventive effect in the absence of excess body fatness.2Lauby-Secretan B Scoccianti C Loomis D et al.Body fatness and cancer—Viewpoint of the IARC Working Group.N Engl J Med. 2016; 375: 794-798Crossref PubMed Scopus (1879) Google Scholar Obesity-related cancer genesis is related to different hormonal mechanisms. Hypotheses explaining the link between obesity and increased cancer risk include sex hormone metabolism, insulin and insulin-like growth factor signalling, adipokine pathophysiology, and obesity-induced low-grade chronic inflammation.3Renehan AG Zwahlen M Egger M Adiposity and cancer risk: new mechanistic insights from epidemiology.Nat Rev Cancer. 2015; 15: 484-498Crossref PubMed Scopus (400) Google Scholar Lymphoma was the predominant haematological cancer in the study. Because a 55% risk reduction of incident lymphoma was found in the surgery group compared with the control group, the authors concluded that lymphoma should be considered an obesity-related cancer type. Notably, in the subgroup analyses, the greatest relative treatment benefit was seen in women with high glucose concentrations. In men, no association of haematological cancer with surgery was seen. The hormonal mechanisms of aromatisation, which involve higher conversion rates of androgenic precursors to oestradiol through increased aromatase enzyme activity in peripheral adipose tissue, might explain this effect. Similarly, to explain these results, hyperinsulinemia, which has direct growth-promoting signalling activity, might indirectly increase free or bioactive insulin-like growth factor.3Renehan AG Zwahlen M Egger M Adiposity and cancer risk: new mechanistic insights from epidemiology.Nat Rev Cancer. 2015; 15: 484-498Crossref PubMed Scopus (400) Google Scholar Bariatric and metabolic surgery, and the associated weight loss, reduce low-grade chronic inflammation, independent of the bariatric surgical procedure.4Chiappetta S Schaack HM Wolnerhannsen B Stier C Squillante S Weiner RA The impact of obesity and metabolic surgery on chronic inflammation.Obes Surg. 2018; 28: 3028-3040Crossref PubMed Scopus (0) Google Scholar Chronic inflammation causes not only cancer, but also life-threatening diseases, such as cardiovascular disease, diabetes, chronic kidney disease, non-alcoholic fatty liver disease, and autoimmune and neurodegenerative disorders.5Furman D Campisi J Verdin E et al.Chronic inflammation in the etiology of disease across the life span.Nat Med. 2019; 25: 1822-1832Crossref PubMed Scopus (1636) Google Scholar It is important to keep in mind that bariatric and metabolic surgery should provide support for a changing lifestyle, which includes physical activity and diet. Therefore, the role of nutrition, nutrigenomics, and fasting should also be highlighted when discussing obesity-associated cancer and cancer prevention. Diet ingredients may change the human genome by altering gene structure or expression, or both.6Nasir A Bullo MMH Ahmed Z et al.Nutrigenomics: epigenetics and cancer prevention: a comprehensive review.Crit Rev Food Sci Nutr. 2020; 60: 1375-1387Crossref PubMed Scopus (52) Google Scholar Dietary anticarcinogens, such as calcium and vitamin D, fruits and vegetables, folate, methionine, and retinoids,6Nasir A Bullo MMH Ahmed Z et al.Nutrigenomics: epigenetics and cancer prevention: a comprehensive review.Crit Rev Food Sci Nutr. 2020; 60: 1375-1387Crossref PubMed Scopus (52) Google Scholar should be included in daily diets. Furthermore, plants, such as apples, broccoli, cashew nuts, citrus, cinnamon, coffee, garlic, grapes, soybeans, tea, tomatoes, and turmeric, may modulate cancer-preventive epigenetic modifications.6Nasir A Bullo MMH Ahmed Z et al.Nutrigenomics: epigenetics and cancer prevention: a comprehensive review.Crit Rev Food Sci Nutr. 2020; 60: 1375-1387Crossref PubMed Scopus (52) Google Scholar When focusing on haematological cancer, the crucial role of hematopoietic stem cells should not be forgotten. As reported by Sjöholm and colleagues,1Sjöholm K Andersson-Assarsson JC Kristensson FM et al.Long-term incidence of haematological cancer after bariatric surgery or usual care in the Swedish Obese Subjects Study: a prospective cohort study.Lancet Healthy Longev. 2023; (published online Sept 13.)https://doi.org/10.1016/S2666-7568(23)00141-1Google Scholar obesity might promote the development of haematological cancers through the increased prevalence of clonal expansion and haematopoiesis induced by somatic mutations in hematopoietic stem cells. Novel evidence suggests that ageing-associated hallmarks of aged hematopoietic stem cells can successfully be ameliorated, or even reverted pharmacologically and genetically. Therefore, the rejuvenation of aged hematopoietic stem cells seems possible.7Guidi N Geiger H Rejuvenation of aged hematopoietic stem cells.Semin Hematol. 2017; 54: 51-55Crossref PubMed Scopus (16) Google Scholar Periodic fasting and fasting-mimicking diets can reduce bodyweight and trunk and total body fat, lower blood pressure, and decrease insulin-like growth factor in humans.8Longo VD Anderson RM Nutrition, longevity and disease: from molecular mechanisms to interventions.Cell. 2022; 185: 1455-1470Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar Fasting-mimicking diet cycles in mice can further activate stem cells, and refeeding with high protein and high calorie nutrition appears to be essential for the regenerative effects in mice.9Cheng C-W Adams GB Perin L et al.Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression.Cell Stem Cell. 2014; 14: 810-823Summary Full Text Full Text PDF PubMed Scopus (308) Google Scholar These results might translate to clinical practice, because calorie restriction after bariatric surgery might have effects similar to fasting. The importance of bariatric surgery in reducing the risk of death by haematological cancer was related by the authors to the improvement in metabolic pathways and the underdosing of chemotherapy in patients with obesity. Difficulties involved in the diagnosis and treatment of all cancer types in patients with obesity should always be kept in mind. In conclusion, we compliment Sjöholm and colleagues for their important results showing that bariatric surgery is associated with a reduced incidence of haematological cancer and the idea that obesity is a significant and modifiable risk factor in haematological cancer. We highlight the importance of dietary changes and the role of nutrigenomics in obesity-associated cancer and cancer prevention. Bariatric and metabolic surgery has been shown to reduce obesity-associated cancers. Future biological and clinical studies regarding the role of food and calorie restriction and nutrigenomics are warranted to complement the global fight against the obesity epidemic and its associated diseases, especially cancer. We declare no competing interests. Long-term incidence of haematological cancer after bariatric surgery or usual care in the Swedish Obese Subjects study: a prospective cohort studyBariatric surgery is associated with a reduced incidence of haematological cancer, specifically in women. Health-care providers and policy makers working in the field of cancer prevention should consider bariatric surgery a primary prevention resource for people with obesity. Full-Text PDF Open Access